Now a days Very-Large-Scale Integrated (VLSI) circuits are facing critical issues to satisfy the cooling demand because of shrinking the semiconductors. In this numerical work, the surface temperature of the chip, heat transfer rate, thermal resistance, power consumption and reliability are studied by using CuO/water nanofluids as coolant and compared the nanofluids results with the results of water. The CuO/water nanofluids at 0.25%, 0.5%, and 0.75% volume concentration are used for this investigation. The modelling, meshing and simulation are carried out by CATIAv5 and ANSYS Fluent v12 CFX software package. It is observed that the heat transfer rates of semiconductor using the coolant CuO/water nanofluid at 0.25%, 0.5%, and 0.75% volume concentrations are 25%, 43%, and 57% respectively higher than that of water. Found that the surface temperature of the semiconductor is lowered by 3%, 6%, and 8%, the thermal resistances decrease up to 6%, 10%, and 13%, and the Nusselt number increases by 25%, 43%, and 56%, when compared to water. It is also studied that the power consumption of the semiconductor reduces by 3%, 6%, and 8% at 0.25%, 0.5%, and 0.75% volume concentration respectively than water as coolant. It is also found that the failure rate of the semiconductor of using CuO/water nanofluids at 0.25%, 0.5%, and 0.75% volume concentration are 69%, 76%, and 84% respectively smaller than the water.